The purpose of this proposal is to gain further insight into the pathophysiology of reactive airway disease by exploring the role played by the potential interactions between physiologic, pharmacologic, immunologic and environmental stimuli that are known to affect airway caliber. The stimuli chosen for study either represent or resemble those found in the environment of all asthmatics and so an appreciation of how they work can have a direct effect on improving patient care. Specifically we wish to determine: (1) if the recently described bronchial challenge of eucapnic hyperventilation with subfreezing air is a more sensitive provocative technique than methacholine in detecting increases in airway reactivity; (2) if the stimulus of airway cooling can interact with a viral upper respiratory tract infection and/or amplify the responses to other constrictor stimuli such as methacholine and antigen provocations; (3) if sympathomimetics and anticholinergics can interact with, or influence, respiratory heat loss; and (4) if inspired air conditions and/or the state of inflammation of the airways can affect aerosol deposition and/or clearance.